OBJECTIVE: To determine the means by which human plaque initiates and maintains a gingival inflammatory reaction. Molecular sieve chromatography of human plaque extracts has resulted in the crude separation of inflammation-inducing components as assessed by the topical application of these fractions to the gingiva of beagle dogs (a model which simulates periodontal disease). Attenuation of the gingival inflammation-inducing activity of these plaque fractions following in vitro treatment with inhibitors such as proteases and spleen extract indicates the presence of heat stable, protease sensitive inflammatory factors. This investigation is designed to further separate and purify the active inflammatory factors in plaque by additional chromatographic and electrophoretic techniques. Initial screening for inflammation-inducing activity will be accomplished with the rat paw edema model and by intradermal testing (dye leakage) in rabbits or guinea pigs. Confirmation of gingival inflammation-inducing activity will be evaluated by topical application to the dog gingiva model and measurement of the crevicular fluid response. Treatment of the active fractions with inhibitors prior to in vivo testing will provide additional information regarding their chemical composition. Active fractions also will be evaluated for biological activities including hyaluronidase, protease, kinin-forming and complement activating properties. Host mechanisms involved in the inflammatory response produced by purified plaque components will be studied. Initiating mechanisms will be studied by pretreatment of the animals with agents such as cobra venom factor and anti-lymphocytic serum. Mediating mechanisms will be investigated by measurement of levels of endogenous mediators (kallikrein, kinin, histamine, prostaglandins) in crevicular fluid and by systemic treatment of the animals with the antagonists of endogenous mediators. The inflammatory parameters measured after treatment will be compared to those in the untreated systems. These studies will provide necessary information for establishing the most effective means of preventing and/or treating periodontal disease.